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• W2914903875 abstract "Pre-mRNA splicing must occur with extremely high fidelity. Spliceosomes assemble onto pre-mRNA guided by specific sequences (5′ splice site, 3′ splice site, and branchpoint). When splice sites are mutated, as in many hereditary diseases, the spliceosome can aberrantly select nearby pseudo- or “cryptic” splice sites, often resulting in nonfunctional protein. How the spliceosome distinguishes authentic splice sites from cryptic splice sites is poorly understood. We performed a Caenorhabditis elegans genetic screen to find cellular factors that affect the frequency with which the spliceosome uses cryptic splice sites and identified two alleles in core spliceosome component Prp8 that alter cryptic splicing frequency. Subsequent complementary genetic and structural analyses in yeast implicate these alleles in the stability of the spliceosome’s catalytic core. However, despite a clear effect on cryptic splicing, high-throughput mRNA sequencing of these prp-8 mutant C. elegans reveals that overall alternative splicing patterns are relatively unchanged. Our data suggest the spliceosome evolved intrinsic mechanisms to reduce the occurrence of cryptic splicing and that these mechanisms are distinct from those that impact alternative splicing." @default.
• W2914903875 created "2019-02-21" @default.
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• W2914903875 date "2019-01-23" @default.
• W2914903875 modified "2023-09-26" @default.
• W2914903875 title "Prp8 impacts cryptic but not alternative splicing frequency" @default.
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• W2914903875 doi "https://doi.org/10.1073/pnas.1819020116" @default.
• W2914903875 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6369775" @default.
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• W2914903875 hasPublicationYear "2019" @default.
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